An Open-label, Single-dose Study to Assess the Pharmacokinetics of Oral Everolimus (Afinitor®) in Subjects With Impaired Hepatic Function

Novartis Pharmaceuticals1 site in 1 country34 target enrollmentNovember 2009

ConditionsHepatic Insufficiency

InterventionsEverolimus

DrugsEverolimus

Overview

Phase: Phase 1
Intervention: Everolimus
Conditions: Hepatic Insufficiency
Sponsor: Novartis Pharmaceuticals
Enrollment: 34
Locations: 1
Primary Endpoint: Evaluate the pharmacokinetics of a single oral dose of everolimus in subjects with severely impaired hepatic function (Child-Pugh C) relative to healthy controls. Measure: AUC, Cmax, tmax, λz, Vd/F, CL/F and t1/2
Status: Completed
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This clinical pharmacology research study will assess the safety and pharmacokinetics of the drug everolimus in patients with impaired hepatic function as compared to healthy volunteers.

Registry

clinicaltrials.gov

Start Date

November 2009

End Date

November 2010

Last Updated

5 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Novartis Pharmaceuticals

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•All subjects:
•In good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory test values (except for values related to hepatic insufficiency).
•Hepatic impaired subjects:
•A Child-Pugh Classification score clinically determined as Class A, Class B, or Class C.
•Absolute neutrophil count (ANC) \> 1000 cells/mm3
•Hemoglobin \> 9 mg/mL
•Platelet count \> 50,000/mm3 at screening and baseline
•Serum creatinine ≤ 2.0 x ULN
•Free of significant medical disorders unrelated to the subject's hepatic disorder

Exclusion Criteria

•All subjects:
•Significant illness, including infections, or hospitalization within 4 weeks prior to dosing (hospitalization is allowed for hepatic impaired subjects if related to liver disease). Invasive systemic fungal infections need to be fully resolved prior to study entry.
•History of acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated).
•History of clinically significant drug allergy; history of atopic allergy (asthma, urticaria, eczematous dermatitis). A known hypersensitivity to the study drug (everolimus) or drugs similar to the study drug (other mTOR inhibitors, e.g., rapamycin or temsirolimus).
•Active bleeding during the last 28 days prior to dosing, including variceal bleeding.
•Except for hepatic impairment, any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs or which may jeopardize the subject in case of participation in the study.
•Use of tobacco within 7 days prior to dosing or during the study.
•Consumption of alcohol within 3 days prior to dosing or during the study.
•Consumption of grapefruits, grapefruit juice, Sevilla oranges, starfruit or related foods within 7 days prior to dosing or during the study period.
•Use of any drugs known to affect CYP3A4 or PgP, including both inhibitors and inducers, within 7 days prior to dosing or during the study.

Arms & Interventions

RAD001

Intervention: Everolimus

Outcomes

Primary Outcomes

Evaluate the pharmacokinetics of a single oral dose of everolimus in subjects with severely impaired hepatic function (Child-Pugh C) relative to healthy controls. Measure: AUC, Cmax, tmax, λz, Vd/F, CL/F and t1/2

Time Frame: First 8 days

Secondary Outcomes

Explore correlation between pharmacokinetics and hepatic function parameters(First 8 days)
Evaluate the pharmacokinetics of a single oral dose of everolimus in subjects with mild and moderate impaired hepatic function (Child-Pugh A and B, respectively) relative to healthy controls.(First 8 days)
Assess the safety and tolerability of a single oral dose of everolimus in subjects with impaired hepatic function (Child-Pugh A, B, and C).(First 8 days plus day 15 and day 28 post-dose follow-ups for safety)